The epidemiology of errors in data capture, management, and analysis: A scoping review of retracted articles and retraction notices in clinical and translational research.

Introduction: To better understand and prevent research errors, we conducted a first-of-its-kind scoping review of clinical and translational research articles that were retracted because of problems in data capture, management, and/or analysis.

Methods: The scoping review followed a preregistered protocol and used retraction notices from the Retraction Watch Database in relevant subject areas, excluding gross misconduct. Abstracts of original articles published between January 1, 2011 and January 31, 2020 were reviewed to determine if articles were related to clinical and translational research.

Individual, social and area level factors associated with older people's walking: Analysis of an UK household panel study (Understanding Society).

Background: Among older people, walking is a popular and prevalent activity. Walking is key to increasing physical activity levels and resulting physical and mental health. In the context of rapidly ageing populations, it is important to better understand what factors are associated with walking among older people, based on the socioecological model of health.

When in the lifecourse? Socioeconomic position across the lifecourse and biological health score.

Purpose: Educational attainment is associated with multiphysiological wear and tear. However, associations with measures of socioeconomic position (SEP) across different life-stages are not established.

Methods: Using regression models and data from 8105 participants from the UK Household Longitudinal Study (Understanding Society), we examined associations of lifecourse SEP with an overall biological health score (BHS).

Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.

Unlabelled: Lynch syndrome (LS) is defined by inherited mutations in DNA mismatch repair genes, including and carries 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, specific mechanisms for LS-associated endometrial carcinogenesis are not well understood. Here, we assessed the effects of MSH2 loss on EC pathogenesis using a novel mouse model (PR-Cre , abbreviated Msh2KO), primary cell lines established from this model, human tissues, and human EC cell lines with isogenic MSH2 knockdown.

A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia.

Background: Severe trauma is associated with systemic inflammation and organ dysfunction. Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma. The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury.

Multicompartmental Trauma Induces Persistent Inflammation and Organ Injury.

Introduction: Previous preclinical models of multicompartmental injury have investigated its effects for durations of less than 72 h and the long-term effects have not been defined. We hypothesized that a model of multicompartmental injury would result in systemic inflammation and multiorgan dysfunction that persists at 1 wk.

Methods: Male and proestrus female Sprague-Dawley rats (n = 16/group) underwent polytrauma (PT) (unilateral right lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures) and were compared to naive controls.

Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials.

Preventing parasite transmission from humans to mosquitoes is recognised to be critical for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs with transmission-blocking properties is a priority. Large screening campaigns have identified many new transmission-blocking molecules, however little is known about how they target the mosquito-transmissible Plasmodium falciparum stage V gametocytes, or how they affect their underlying cell biology.

NARROWING THE GAP: PRECLINICAL TRAUMA WITH POSTINJURY SEPSIS MODEL WITH INCREASED CLINICAL RELEVANCE.

Background : Overall outcomes for trauma patients have improved over time. However, mortality for postinjury sepsis is unchanged. The use of relevant preclinical studies remains necessary to understand mechanistic changes after injury and sepsis at the cellular and molecular level.

Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven by Different p53 Mutants.

Unlabelled: Missense mutations in the DNA binding domain of p53 are characterized as structural or contact mutations based on their effect on the conformation of the protein. These mutations show gain-of-function (GOF) activities, such as promoting increased metastatic incidence compared with p53 loss, often mediated by the interaction of mutant p53 with a set of transcription factors. These interactions are largely context specific.

Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program.

Unlabelled: Cancer-related alterations of the p53 tetramerization domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers, which are also normal p53 states under basal cellular conditions. However, their physiologic relevance is not well understood.

Multicompartmental traumatic injury induces sex-specific alterations in the gut microbiome.

Background: Previous preclinical studies have demonstrated an altered gut microbiome after traumatic injury; however, the impact of sex on dysbiosis remains unknown. We hypothesized that the "pathobiome" phenotype induced by multicompartmental injuries and chronic stress is host sex specific with unique microbiome signatures.

Methods: Male and proestrus female Sprague-Dawley rats (n = 8/group) aged 9 weeks to 11 weeks were subjected to either multicompartmental injury (PT) (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures), PT plus 2 hours daily chronic restraint stress (PT/CS) or naive controls.

Alendronate conjugate for targeted delivery to bone-forming prostate cancer.

Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.

Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity.

Impact of subjective and objective neighbourhood characteristics and individual socioeconomic position on allostatic load: A cross-sectional analysis of an all-age UK household panel study.

Research suggests that individuals living in more disadvantaged neighbourhoods experience higher levels of stress but this has generally been based on self-reported stress. We used survey-based neighbourhood quality indicators and biomarker data from Understanding Society, linked to census and crime statistics to explore associations of allostatic load (AL), an objective biomarker-based measure of cumulative stress, with subjective and objective neighbourhood characteristics. Analyses of 6887 respondents living in England show greater AL among those living in more disadvantaged areas, with objective measure associations stronger than subjective.

Multicompartmental traumatic injury and the microbiome: Shift to a pathobiome.

Background: Previous animal models have demonstrated altered gut microbiome after mild traumatic injury; however, the impact of injury severity and critical illness is unknown. We hypothesized that a rodent model of severe multicompartmental injuries and chronic stress would demonstrate microbiome alterations toward a "pathobiome" characterized by an overabundance of pathogenic organisms, which would persist 1 week after injury.

Methods: Male Sprague-Dawley rats (n = 8 per group) were subjected to either multiple injuries (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus daily chronic restraint stress for 2 hours (PT/CS), or naive controls.

Examining the impact of different social class mechanisms on health inequalities: A cross-sectional analysis of an all-age UK household panel study.

Background: Socioeconomic inequalities are well established across health, morbidity and mortality measures. Social class theory describes how social groups relate, interact and accrue advantages/disadvantages relative to one another, with different theorists emphasising different dimensions. In the context of health inequalities, different social class measures are used interchangeably to rank population groups in terms of health rather than directly exploring the role of social class in creating inequalities.

Context matters - Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas.

Genome sequencing has revealed the importance of epigenetic regulators in tumorigenesis. The genes encoding the chromatin remodeling complex DAXX:ATRX are frequently mutated in pancreatic neuroendocrine tumors; however, the underlying mechanisms of how mutations contribute to tumorigenesis are only partially understood, in part because of the lack of relevant preclinical models. Here, we used genetically engineered mouse models combined with environmental stress to evaluate the tumor suppressor functions of Daxx and Atrx in the mouse pancreas.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Bismuth Nanoparticle and Polyhydroxybutyrate Coatings Enhance the Radiopacity of Absorbable Inferior Vena Cava Filters for Fluoroscopy-Guided Placement and Longitudinal Computed Tomography Monitoring in Pigs.

Inferior vena cava filters (IVCFs) constructed with poly--dioxanone (PPDO) are promising alternatives to metallic filters and their associated risks and complications. Incorporating high-Z nanoparticles (NPs) improves PPDO IVCFs' radiopacity without adversely affecting their safety or performance. However, increased radiopacity from these studies are insufficient for filter visualization during fluoroscopy-guided PPDO IVCF deployment.

Differential Gain-of-Function Activity of Three p53 Hotspot Mutants In Vivo.

Unlabelled: The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance.

The evolutionary ecology of age at natural menopause: implications for public health.

Evolutionary perspectives on menopause have focused on explaining why early reproductive cessation in females has emerged and why it is rare throughout the animal kingdom, but less attention has been given to exploring patterns of diversity in age at natural menopause. In this paper, we aim to generate new hypotheses for understanding human patterns of diversity in this trait, defined as age at final menstrual period. To do so, we develop a multilevel, interdisciplinary framework, combining proximate, physiological understandings of ovarian ageing with ultimate, evolutionary perspectives on ageing.

Effect of bead size and doxorubicin loading on tumor cellular injury after transarterial embolization and chemoembolization in a rat model of hepatocellular carcinoma.

Embolic agents used in transarterial embolization for intermediate stage hepatocellular carcinoma reduce blood flow into tumors and can deliver anticancer drugs. Tumor blood supply can be interrupted using doxorubicin-eluting beads (DEB-TACE) or non-loaded beads (TAE) of different calibers. In this preclinical study, we characterized the extent of remaining stressed tumor cells after treatment, hypoxia within the surviving tumor regions, and inflammatory immune cell infiltrates after embolization with 40-60 or 70-150 μm with non-loaded or doxorubicin-loaded beads at 3 and 7 days after treatment.

Standard multiple imputation of survey data didn't perform better than simple substitution in enhancing an administrative dataset: the example of self-rated health in England.

Background: Health surveys provide a rich array of information but on relatively small numbers of individuals and evidence suggests that they are becoming less representative as response levels fall. Routinely collected administrative data offer more extensive population coverage but typically comprise fewer health topics. We explore whether data combination and multiple imputation of health variables from survey data is a simple and robust way of generating these variables in the general population.